Asthma is known to run in families, but the genetic mechanisms involved in its pathogenesis are not well understood. The study of thee mechanism requires an understanding of the factors associated with and predisposing to the development of the disease. Several intermediate phenotypes for asthma have been described relating to: total serum IgE levels, bronchial hyperresponsiveness, susceptibility to become sensitized to aeroallergens and baseline airway function (as assessed by spirometry). In addition, segregation analyses have been performed on the families that support the hypothesis that total serum IgE levels are controlled by a major autosomal codominant gene. The aims of this proposal are: to perform linkage analysis of this putative gene for total IgE levels with candidate genes and with highly polymorphic markers whose location in the human genome is known; and to determine by segregation analysis if a monogenic component is involved in the inheritance of bronchial hyperresponsiveness, baseline airway function, and susceptibility to become sensitized to multiple aeroallergens. These studies will allow a better understanding of the pathogenesis of asthma and help in this prevention and treatment.